D-serine accelerates gastric tumor growth by suppressing killer T cells
One of the crucial steps in cancer proliferation is evading killer immune cells. Cancer cells use a variety of signaling molecules to evade the immune system. Immune checkpoint inhibitor (ICI) therapy interferes with some of these evasion tactics, improving the immune system's ability to suppress tumors. However, the success of ICI therapy depends on the specific signals being secreted by the…
Gastric cancer (GC) appears to advance more rapidly when D-serine, an unusual signaling molecule, is present. Researchers from Keio University School of Medicine have discovered that introducing D-serine into mouse models of GC resulted in significantly faster tumor growth compared to control groups. This effect was attributed to D-serine's powerful immunosuppressive qualities.
The molecule increased anti-inflammatory immune cells and M2-like macrophages in the tumor environment, leading to a notable decrease in the presence and activity of CD8+ cytotoxic T cells, responsible for killing cancer cells. Furthermore, tumor-associated macrophages released excessive amounts of two immunosuppressive molecules, fibronectin 1 and secreted phosphoprotein 1, which suppressed CD8+ T cells.
When treatment with anti-SPP1 antibodies was administered to D-serine-enhanced tumors, tumor growth dropped to levels similar to those in low-D-serine conditions. Additionally, the study found that GC patients with higher serum D-serine concentrations faced more resistance to immune checkpoint inhibitor therapy. This suggests that D-serine may serve as a potential biomarker for GC development and immune checkpoint inhibitor resistance.
The findings propose that targeting D-serine and its associated signaling pathways could lead to new treatments for gastric cancer and improve the efficacy of immune checkpoint inhibitor therapies.
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